Germ line variants in patients with acute myeloid leukemia without a suspicion of hereditary hematologic malignancy syndrome

Blood Advances - Tập 7 - Trang 5799-5811 - 2023
Francesca Guijarro1,2, Monica López-Guerra1,2,3, Jordi Morata4, Alex Bataller2,5, Sara Paz1, Josep Maria Cornet-Masana6, Antònia Banús-Mulet6, Laia Cuesta-Casanovas6, Josep Maria Carbó6, Sandra Castaño-Díez2,5, Carlos Jiménez-Vicente2,5, Albert Cortés-Bullich2,5, Ana Triguero2,5, Alexandra Martínez-Roca2,5, Daniel Esteban2,5, Marta Gómez-Hernando1,2, José Ramón Álamo Moreno1, Irene López-Oreja1,2, Marta Garrote1,2, Ruth M. Risueño6
1Pathology Department, Hematopathology Section, Hospital Clínic Barcelona, Barcelona, Spain
2Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
3Centro de Investigación Biomédica en Red de Cáncer, Madrid, Spain
4Centro Nacional de Análisis Genómico, Barcelona, Spain
5Hematology Department, Hospital Clínic Barcelona, Barcelona, Spain
6Josep Carreras Leukaemia Research Institute, Barcelona, Spain

Tóm tắt

Abstract Germ line predisposition in acute myeloid leukemia (AML) has gained attention in recent years because of a nonnegligible frequency and an impact on management of patients and their relatives. Risk alleles for AML development may be present in patients without a clinical suspicion of hereditary hematologic malignancy syndrome. In this study we investigated the presence of germ line variants (GVs) in 288 genes related to cancer predisposition in 47 patients with available paired, tumor-normal material, namely bone marrow stroma cells (n = 29), postremission bone marrow (n = 17), and saliva (n = 1). These patients correspond to 2 broad AML categories with heterogeneous genetic background (AML myelodysplasia related and AML defined by differentiation) and none of them had phenotypic abnormalities, previous history of cytopenia, or strong cancer aggregation. We found 11 pathogenic or likely pathogenic variants, 6 affecting genes related to autosomal dominant cancer predisposition syndromes (ATM, DDX41, and CHEK2) and 5 related to autosomal recessive bone marrow failure syndromes (FANCA, FANCM, SBDS, DNAJC21, and CSF3R). We did not find differences in clinical characteristics nor outcome between carriers of GVs vs noncarriers. Further studies in unselected AML cohorts are needed to determine GV incidence and penetrance and, in particular, to clarify the role of ATM nonsense mutations in AML predisposition.

Tài liệu tham khảo

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